OBJECTIVES: This study sought to assess the presence of a dose-response effect of cigarette smoking and its impact on high on-treatment platelet reactivity (HPR) in patients with diabetes mellitus treated with clopidogrel. BACKGROUND: Cigarette smoking is an inducer of cytochrome P450 1A2, a hepatic enzyme involved in clopidogrel metabolism. If cigarette smoking is associated with a dose-response effect on pharmacodynamic measures in clopidogrel-treated patients is unknown. METHODS: A total of 134 type 2 diabetes mellitus patients on maintenance aspirin and clopidogrel therapy were studied. Patients were divided into 3 groups according to cotinine levels: <3 ng/ml (nonsmokers), 3 to 199 ng/ml (light smokers), and ≥ 200 ng/ml (heavy smokers). Platelet function was assessed by light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetrics, San Diego, California), and vasodilator-stimulated phosphoprotein. Rates of HPR were defined using established cutoff values. RESULTS: A dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with platelet reactivity as assessed by light transmittance aggregometry using 5 and 20 μmol/l adenosine diphosphate (p < 0.0001 for all). Accordingly, platelet disaggregation increased with levels of serum cotinine (p < 0.0001). Similar results were found with P2Y(12) reaction units (p < 0.0001) and inhibition of platelet aggregation (p = 0.005) as defined by VerifyNow P2Y12 testing, and platelet reactivity index (p = 0.002) as assessed by vasodilator-stimulated phosphoprotein. Higher serum cotinine levels were significantly associated with lower rates of HPR, as defined according to various pharmacodynamic cutoff measures. CONCLUSIONS: Cigarette smoking is associated with a dose-response effect on clopidogrel-induced antiplatelet effects and lower rates of HPR in diabetes mellitus patients. Copyright Â
OBJECTIVES: This study sought to assess the presence of a dose-response effect of cigarette smoking and its impact on high on-treatment platelet reactivity (HPR) in patients with diabetes mellitus treated with clopidogrel. BACKGROUND: Cigarette smoking is an inducer of cytochrome P450 1A2, a hepatic enzyme involved in clopidogrel metabolism. If cigarette smoking is associated with a dose-response effect on pharmacodynamic measures in clopidogrel-treated patients is unknown. METHODS: A total of 134 type 2 diabetes mellituspatients on maintenance aspirin and clopidogrel therapy were studied. Patients were divided into 3 groups according to cotinine levels: <3 ng/ml (nonsmokers), 3 to 199 ng/ml (light smokers), and ≥ 200 ng/ml (heavy smokers). Platelet function was assessed by light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetrics, San Diego, California), and vasodilator-stimulated phosphoprotein. Rates of HPR were defined using established cutoff values. RESULTS: A dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with platelet reactivity as assessed by light transmittance aggregometry using 5 and 20 μmol/l adenosine diphosphate (p < 0.0001 for all). Accordingly, platelet disaggregation increased with levels of serum cotinine (p < 0.0001). Similar results were found with P2Y(12) reaction units (p < 0.0001) and inhibition of platelet aggregation (p = 0.005) as defined by VerifyNow P2Y12 testing, and platelet reactivity index (p = 0.002) as assessed by vasodilator-stimulated phosphoprotein. Higher serum cotinine levels were significantly associated with lower rates of HPR, as defined according to various pharmacodynamic cutoff measures. CONCLUSIONS: Cigarette smoking is associated with a dose-response effect on clopidogrel-induced antiplatelet effects and lower rates of HPR in diabetes mellituspatients. Copyright Â
Authors: Jung Rae Cho; Bhaloo Desai; Michael J Haas; Fabiana Rollini; Francesco Franchi; Ana Muñiz-Lozano; Antonio Tello-Montoliu; Elisabetta Ferrante; Luis A Guzman; Theodore A Bass; Dominick J Angiolillo Journal: J Cardiovasc Transl Res Date: 2013-12-20 Impact factor: 4.132
Authors: Fabiana Rollini; Francesco Franchi; Jung Rae Cho; Christopher Degroat; Mona Bhatti; Elisabetta Ferrante; Ronakkumar Patel; Andrew Darlington; Antonio Tello-Montoliu; Bhaloo Desai; Joséluis Ferreiro; Ana Muniz-Lozano; Martin M Zenni; Luis A Guzman; Theodore A Bass; Dominick J Angiolillo Journal: J Cardiovasc Transl Res Date: 2014-01-07 Impact factor: 4.132
Authors: Daniel J Conklin; Suzaynn Schick; Michael J Blaha; Alex Carll; Andrew DeFilippis; Peter Ganz; Michael E Hall; Naomi Hamburg; Tim O'Toole; Lindsay Reynolds; Sanjay Srivastava; Aruni Bhatnagar Journal: Am J Physiol Heart Circ Physiol Date: 2019-02-01 Impact factor: 4.733